Prof.S.SUNDAR’S unitDr.G.Rengaraj.PG

History

Mrs. Kalyani, a 60 yr female came with c/o difficulty in swallowing – 2 years - more for solid foods - persistent -not progressive no h/o drooling of food or saliva no h/o nasal regurgitation of food no h/o hoarseness of voice no h/o vomiting h/o dryness of mouth – 2 yrs

History h/o dryness of both eyes – 2 yrs - asso. With gritty sensation in both eyes

- diff. in opening both eyes in morning

no h/o redness of eyes h/o pain in both knee joint – 6 weeks - more during activity, relieved by rest - no diurnal variation - no h/o any swelling in the joints - no h/o any other joint involvement

History no h/o any chronic drug intakeNot a known DM/HTNo h/o any surgery or irradiationNo h/o jaundiceNo positive family historyPM – attained menopause at 50 yrs of ageh/o cataract surgery done for both eyes 5 yrs

before

ExaminationO/E pt. conscious, oriented,afebrile no P/Ict./Cy./Cl./nodes/PE dry tongue + BP- 120/74 , P – 78/min CVS- S1 S2 + , no murmurs RS – NVBS + , no added sounds P/A – soft , no organomegaly CNS – NFND Both eyes – Normal

DD of sicca symptomsXerostomia Viral infectionsDrugs :

1.antihypertensive 2.parasympatholyticDMTraumaSjogren’s

Dry eyeInflammation: 1.chronic

conjunctivitis 2.chronic blepharitis 3. SJS 4. Pemphigoid 5. sjogren’s syn.Toxicity 1. Burns 2. drugs Misc. 1.trauma 2. hypovitaminosis A

INVESTIGATIONSInv. Hb- 10.0 Sugar – 133 PCV – 3O urea - 22 RBC – 3 millions/ml creatinine –

0.8 TC – 7000 Na – 138 DC – P67L30 E3 k - 4.6 ESR – 15 / 30 Bicarb - 22 Plt. – 2 lakhs/ ml Cl – 98 MCV - 92 MCH- 32 MCHC - 30

Inv.Urine r/e alb – nil sugar- nil deposits- 1-2 pus cells/hpf FBS – 78 , PPBS – 104CXR – NormalECG – Normal X-ray both knee – normal PS – Normocytic normochromic anemia +

Ophthal op. Rt. Eye Left eyeAS N NPupils irregular,sluggish RTL irregular,

RTL Lens pseudophakia

pseudophakiaRefr. 6/24 5/60 with PH no inc. in power 6/24SCHIRMERS TEST 2 mm 2 mm imp - sugg. of DRY EYE

INV.RF – POS.ANA - neg

Anti – SS-A - Positive Anti – SS-B - Negative

Biopsy Lower lip biopsy:Microscopic description:

skin lined by hyperkeratotic,hyperplastic squamous epithelium with underlying dermis showing inflammatory cell infiltrate,congested blood vessels, basal layers showing basilar vacuolisation & edema of the dermis

Impression: consistent with sjogren’s syndrome

Inv.Anti-HCV – neg.HIV – non-reactiveCT Chest – normalACLA – neg

Sjogren’s syndrome Revised International Classification Criteria for Sjögren's Syndrome I. Ocular symptoms: a positive response to at least one of the following

questions: Have you had daily, persistent, troublesome dry eyes for more than 3

months? Do you have a recurrent sensation of sand or gravel in the eyes? Do you use tear substitutes more than 3 times a day?

 II. Oral symptoms: a positive response to at least one of the following questions:

Have you had a daily feeling of dry mouth for more than 3 months? Have you had recurrently or persistently swollen salivary glands as an

adult? Do you frequently drink liquids to aid in swallowing dry food?

criteriaIII. Ocular signs-that is, objective evidence of ocular

involvement defined as a positive result for at least one of the following two tests:

Schirmer's I test, performed without anaesthesia (</=5 mm in 5 minutes)

Rose bengal score or other ocular dye score (>/=4 according to van Bijsterveld's scoring system)

 IV. Histopathology: In minor salivary glands (obtained through normal-appearing mucosa) focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score >/=1, defined as a number of lymphocytic foci (which are adjacent to normal-appearing mucous acini and contain more than 50 lymphocytes) per 4 mm2 of glandular tissue

CRITERIAV. Salivary gland involvement: objective evidence of

salivary gland involvement defined by a positive result for at least one of the following diagnostic tests:

Unstimulated whole salivary flow (</=1.5 ml in 15 minutes)

Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary or destructive pattern), without evidence of obstruction in the major ducts

Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed excretion of tracer

 VI. Autoantibodies: presence in the serum of the

following autoantibodies:Antibodies to Ro(SSA) or La(SSB) antigens, or both

Criteria Revised Rules for Classification   For primary SS In patients without any potentially associated disease, primary SS may be defined as follows: The presence of any 4 of the 6 items is indicative of primary SS, as long as either item IV

(Histopathology) or VI (Serology) is positive The presence of any 3 of the 4 objective criteria items (that is, items III, IV, V, VI) The classification tree procedure represents a valid alternative method for classification, although it

should be more properly used in clinical-epidemiological survey   For secondary SS In patients with a potentially associated disease (for instance, another well defined connective

tissue disease), the presence of item I or item II plus any 2 from among items III, IV, and V may be considered as indicative of secondary SS

  Exclusion criteria: Past head and neck radiation treatment Hepatitis C infection Acquired immunodeficiency disease (AIDS) Pre-existing lymphoma Sarcoidosis Graft versus host disease Use of anticholinergic drugs

Picture showing DRY,ERYTHEMATOUS ORAL MUCOSA of the ptThe pt. had h/o dry mouth daily for 2 yrs & frequently drinking liquids to aid in swallowing solid food – satisfying item 2 of the criteria

Sjogren’sIt is a chronic,slowly progressive autoimmune

disease characterised by lymphocytic infiltration of the exocrine glands.

Middle-aged women are primarily affected, but it can occur in all ages,including childhood

F:M = 9:1Prevalence – 0.5 to 1.0 %30 % of pts with autoimmune rheumatic disease

suffers from secondary sjogrens syn.Approx. 1/3rd of pts present with systemic

manifestations

Pathogenesis Autoimmune disease Both T cell lymphocytic infiltration of exocrine

glands & B cell lymphocytic hyperreactivity.Infiltrating lymphocytes provide apoptotic

signals to the epithelial cells.The serum contains autoantibodies directed

against non-organ-specific antigens such as immunoglobulins(RF) & extractable nuclear and cytoplasmic antigens ( Ro/SS-A, La/SS-B )

HLA-B8, DR3 & DRw52 are prevalent in pts with primary sjogren’s.

Clinical manifestationsMajority of pts have symptoms related to

diminished lacrimal & salivary gland functionIn most pts the primary syndrome runs a

slow & benign coursePredominant Glandular manifestations: xerostomia keratoconjunctivitis sicca other less frequent glandular

manifestations: xerotrachea,atrophic gastritis,subclinical

pancreatitis

Clinical.Extra-glandular manifestations are seen in one-third of pts:

low-grade fever raynaud’s phenomenon myalgia arthralgiaMost pts with primary sjogrens experience atleast

one episode of nonerosive arthritisrenal involvement – interstitial nephritis clinically

manifesting as hypoasthenuriaSN hearing loss was found in one-half of pts with

sjogrensVasculitis – purpura, recurrent urticaria, skin ulcers ILD

Clinical.A small but significant pts. Develop

malignant lymphoma. The features sugg. The development of lymphoma are:

persistent parotid enlargement purpura leukopenia cryoglobulinemiaMost lymphomas are extra-nodal marginal

zone B cell lymphomas & are usually detected incidentally during evaluation of labial biopsy

DiagnosisThe diagnosis of primary sjogren’s syndrome is

obtained if 1)the patient presents with eye and/or mouth

dryness, 2)the eye tests disclose keratoconjunctivitis sicca, 3)the mouth evaluation reveals classic

manifestations of the syndrome, and 4) the pt serum reacts with Ro/SS-A and/or La/SS-B

autoantigensLabial biopsy is needed when the diagnosis is

uncertain or to rule out other conditionsHCV infection should be ruled out since apart from

SEROLOGIC TESTS the remainder of the clinico-pathologic picture is almost identical to that of sjogren’s

DD of sjogren’s HIV infection & sicca syndrome

sjogren’s syn.

sarcoidosis

Age predominantly young males

predominantly in middle-aged women

invariable

Auto-antibodies - Presence of autoantibodies to Ro/SS-A and/or La/SS-B

-

Histology lymphoid infiltrates of salivary glands by CD8+ lymphocytes

Lymphoid infiltrates of salivary glands by CD4+ lymphocytes

granulomas in salivary glands

Genetics Associated with HLA-DR5

Associated with HLA-DR3 & DRw52

unknown

Serology Positive tests for HIV

Neg. tests Neg. tests

HIV & Sjogren’sImmunologic & rheumatologic disorders are common in

HIV ptsDrug allergies are the most significant allergic

reactions in HIV + , more common as the disease progresses(upto 65% for TMP/SMX)

SLE & RA are ameliorated by the concomitant HIV inf.The one autoimmune disease that may occur with

increased frequency in HIV inf. Is A VARIANT of PRIMARY SJOGREN’S

This syn. Consists of parotid gland enlargement,dry eyes & dry mouth

These pts donot have anti-SS-A or anti-SS-BLess common with increased use of ARVThe term DIFFUSE INFILTRATIVE LYMPHOCYTOSIS

SYNDROME(DILS) is used to describe this entity

Treatment Glandular manifestations:Dry eyes:1.Artificial tears without preservatives 2.avoidance of drugs that decrease

lacrimal & salivary secretion such as diuretics, antihypertensive drugs,anticholinergics & antidepressants.

3. systemic stimulation with oral pilocarpine 5 mg TID,oral cevimeline 30 mg TID

4. Severe dry eyes: NL duct occlusion ,soft contact lenses, corneal transplantation

Treatment Xerostomia:Lubrication – water( the best replacement)Local stimulation- flavoured lozenges or gumSystemic stimulation – as for dry eyesTopical application of fluorideOral candidiasis – topical nystatin or

clotrimazole lozengesParotid enlargement : Treat superinfection- antibiotics,analgesicsHard, persistent – r/o lymphoma

Treatment Extraglandular manifestations:Arthritis: Hydroxychloroquine 200-400 mg/day Raynaud’s : cold protection with gloves &

T.Nifedipine 10 mg TDSRTA : Bicarbonate replacementLymphoma : CHOP + anti-CD20Systemic vasculitis: glucocorticoids 1 mg/kg

per day

Secondary sjogren’sWhen it presents in association with other

autoimmune rheumatic diseasesThe common autoimmune diseases associated

with sjogren’s are: 1. Rheumatoid arthritis 2. SLE 3. Scleroderma 4. MCTD 5. Primary biliary cirrhosis 6. vasculitis 7. chronic active hepatitis